Epitope Spreading Is Rarely Found in Pemphigus Vulgaris by Large-Scale Longitudinal Study Using Desmoglein 2-Based Swapped Molecules
Epitope Spreading Is Rarely Found in Pemphigus Vulgaris by Large-Scale Longitudinal Study Using Desmoglein 2-Based Swapped Molecules
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DOI：
10.1038/jid.2011.448
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发表时间：
2012-04-01
影响因子：
6.5
通讯作者：
Hashimoto, Takashi
中科院分区：
文献类型：
--
作者：
Ohyama, Bungo;Nishifuji, Koji;Hashimoto, Takashi
表位扩散涉及诱导和维持自身反应性。寻常型天疱疮(PV)的表位扩散是由抗桥粒芯糖蛋白3(Dsg3)和DSG1的自身抗体引起的，以前利用Dsg3/DSG1胞外区互换的分子来分析。然而，仅使用这种方法精确识别每个分子中的负责表位是有问题的。在本研究中，我们利用Dsg3(或Dsg1)/Dsg2结构域交换分子，通过免疫沉淀-免疫印迹的方法研究了抗原表位在PV中的扩散，克服了以往方法中存在的问题。我们分析了53例不同疾病阶段的PV患者的212份血清识别的抗原表位。抗Dsg3黏膜显性型PV和抗Dsg3/DSG1黏膜皮肤型PV的主要表位存在于DsGs的N端，且在病程中没有变化。这些N端表位依赖于钙离子。副肿瘤性天疱疮和疱疹状天疱疮的循环抗体有独特的表位分布，尽管DSG N末端仍然包含主要表位。这些结果表明，在PV发病后，Dsg3和DSG1上的分子内和分子间表位在胞外区之间的扩散在PV中是罕见的，并且与病程无关。
Epitope spreading is involved in inducing and maintaining self-reactivity. Epitope spreading in pemphigus vulgaris (PV), caused by IgG autoantibodies to desmoglein 3 (Dsg3) and Dsg1, was previously analyzed using Dsg3/Dsg1 extracellular domain-swapped molecules. However, precise identification of the responsible epitopes in each molecule by using only this method was problematic. In this study, we studied epitope spreading in PV by a novel immunoprecipitation-immunoblot method using Dsg3 (or Dsg1)/Dsg2 domain-swapped molecules, which overcomes the problems associated with the previous approaches. We analyzed the antigenic epitopes recognized by 212 sera collected from 53 PV patients at multiple disease stages. The major epitopes were present at the N-terminal region of Dsgs and were unchanged over the course of the disease in both anti-Dsg3 mucosal dominant-type PV and anti-Dsg3/Dsg1 mucocutaneous-type PV. These N-terminal epitopes were calcium dependent. Circulating antibodies in paraneoplastic pemphigus and pemphigus herpetiformis had unique epitope distributions, although the Dsg N-termini still contained the major epitopes. These results suggest that, after onset, intramolecular and intermolecular epitope spreading among extracellular domains on Dsg3 and Dsg1 is rare in PV and has no correlation with disease course.